19-17278895-G-T

Variant names:

• chr19-17278895-G-T
• NM_014173.4:c.837G>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014173.4(BABAM1):​c.837G>T​(p.Lys279Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: BABAM1 NM_014173.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.06

Genes affected

BABAM1 (HGNC:25008): (BRISC and BRCA1 A complex member 1) Involved in several processes, including mitotic G2 DNA damage checkpoint signaling; positive regulation of DNA repair; and protein K63-linked deubiquitination. Located in cytosol and nuclear body. Part of BRCA1-A complex and BRISC complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000269307 (HGNC:):

USHBP1 (HGNC:24058): (USH1 protein network component harmonin binding protein 1) Enables PDZ domain binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32602733).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BABAM1	NM_014173.4	c.837G>T	p.Lys279Asn	missense_variant	Exon 9 of 9	ENST00000598188.6	NP_054892.2
BABAM1	NM_001033549.3	c.837G>T	p.Lys279Asn	missense_variant	Exon 9 of 9		NP_001028721.1
BABAM1	NM_001288756.2	c.837G>T	p.Lys279Asn	missense_variant	Exon 9 of 9		NP_001275685.1
BABAM1	NM_001288757.2	c.612G>T	p.Lys204Asn	missense_variant	Exon 6 of 6		NP_001275686.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BABAM1	ENST00000598188.6	c.837G>T	p.Lys279Asn	missense_variant	Exon 9 of 9	1	NM_014173.4	ENSP00000471605.1
ENSG00000269307	ENST00000596542.1	n.*400+1986G>T		intron_variant	Intron 7 of 9	2		ENSP00000469159.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.79
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.041	T;T;T;T;T
Eigen	Benign	-0.0075
Eigen_PC	Benign	0.056
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.88	.;D;.;D;.
M_CAP	Benign	0.0096	T
MetaRNN	Benign	0.33	T;T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	M;.;M;M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.97	.;.;N;.;.
REVEL	Benign	0.038
Sift	Benign	0.038	.;.;D;.;.
Sift4G	Benign	0.30	T;T;T;T;T
Polyphen		0.53	P;.;P;P;.
Vest4		0.47
MutPred		0.30		Loss of ubiquitination at K279 (P = 0.0192);.;Loss of ubiquitination at K279 (P = 0.0192);Loss of ubiquitination at K279 (P = 0.0192);.;
MVP		0.30
MPC		0.60
ClinPred		0.49	T
GERP RS		2.8
Varity_R		0.24
gMVP		0.32

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17389704;